Correlations of developmental end points observed after 2,4,5‐trichlorophenoxyacetic acid exposure in mice

Abstract

A large-scale developmental toxicology study of 2,4,5-trichlorophenoxyacetic acid was conducted in four inbred strains and one outbred strain of mice. The most significant developmental effects observed were reduced fetal weight and increased incidences of cleft palate (malformation) and prenatal death (deaths/resorptions). The correlation coefficients among the proportion of deaths/resorptions, proportion of malformations, average fetal weights, and number of viable fetuses were investigated, with each variable measured on a per-litter basis. Generally, the correlation coefficients between average fetal weight and number of viable fetuses were negative for the control and low-dose groups in the C57BL/6, C3H/He, and BALB/c strains. Overall, the correlation coefficients between proportion of malformations and number of viable fetuses were not significant. The correlation coefficients between proportion of malformations and average fetal weight were negative for all but one case. The correlations were weak in the control and low-dose groups, in which the malformation rates were very low, and were strong in the high-dose groups. The correlation coefficients between proportion of deaths/resorptions and proportion of malformations were generally positive at the high doses; some negative correlations were observed in control and low-dose groups. The correlation coefficients between proportion of deaths/resorptions and average fetal weight were negative for the A/JAX and CD-1 strains. In summary, the strongest relationship observed was the negative correlation between fetal weight and malformation.

Likelihood Models for Clustered Binary and Continuous Out comes: Application to Developmental Toxicology

“…One approach (Catalano et al, 1993) considers the nonlive and live outcomes as being conditionally independent; hence, they can be modeled separately. However, the live outcomes are correlated (Ryan et al, 1991;Chen and Gaylor, 1992), so that " Indicates the number of animals that exhibit one or more malformations.…”

Dose-Response Modelling of Growth for Developmental Toxicity

“…(1991) and Chen and Gaylor (1992) demonstrated a relationship between normal foetuses in rodents and foetal weight and suggested that some malformations may result from inadequate growth. Thus, the ratio N ( d , t ) / N ( O , t ) is used as a basis for a dose-response modelling of developmental effect.…”

Markov counting models for correlated binary responses

“…Researchers exposed pregnant mice to different doses of the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) during gestation and recorded the number of implanted fetuses and the number of fetuses that died, were resorbed, or had a cleft palate (Holson and others, 1992;Chen and Gaylor, 1992). They observed the number of implanted fetuses, number of "affected" fetuses, and the dose of 2,4,5-T for each mouse in the experiment and are given in Table 1 of George and Bowman (1995).…”